[Fascinating] Depression: An Evolutionary Byproduct of Immune System?

This study is fascinating because it ties depression to evolution. Depression could be a way to adapt and survive infections. Interesting is also the outcome. The scientists say that people with depression have higher inflammation markers although they don't seem to be infected. This raises the question if inflammation alone can also lead to depression. However, their statement is not easy to prove in my eyes. How do they test for infections? There are probably thousands of different infections and I highly doubt that we have the diagnostic means to test for all of them. In the end however it's still very interesting that depression can be absolutely independent from psychological factors. Depression can be a pure physical disease and nothing else. It's time that psychologist accept this and stop using all kinds of crazy, unscientific and wrong explanations for their patients' burden.

Fever, fatigue/inactivity, social avoidance and anorexia can all be seen as adaptive behaviors in light of the need to contain infection, they write.

Click to expand...

So if a person stayed away from other people because he was depressed, this reduced his risk of getting infected by these other humans if they were ill. Fascinating.

Depression: An Evolutionary Byproduct of Immune System?
ScienceDaily (Mar. 1, 2012) Depression is common enough -- afflicting one in ten adults in the United States -- that it seems the possibility of depression must be "hard-wired" into our brains. This has led biologists to propose several theories to account for how depression, or behaviors linked to it, can somehow offer an evolutionary advantage.

Some previous proposals for the role of depression in evolution have focused on how it affects behavior in a social context. A pair of psychiatrists addresses this puzzle in a different way, tying together depression and resistance to infection. They propose that genetic variations that promote depression arose during evolution because they helped our ancestors fight infection.
An outline of their proposal appears online in the journal Molecular Psychiatry.
The co-authors are Andrew Miller, MD, William P. Timmie professor of psychiatry and behavioral sciences at Emory and director of psychiatric oncology at Winship Cancer Institute, and Charles Raison, MD, previously at Emory and now at the University of Arizona.For several years, researchers have seen links between depression and inflammation, or over-activation of the immune system. People with depression tend to have higher levels of inflammation, even if they're not fighting an infection.
"Most of the genetic variations that have been linked to depression turn out to affect the function of the immune system," Miller says. "This led us to rethink why depression seems to stay embedded in the genome."
"The basic idea is that depression and the genes that promote it were very adaptive for helping people -- especially young children -- not die of infection in the ancestral environment, even if those same behaviors are not helpful in our relationships with other people," Raison says.
Infection was the major cause of death in humans' early history, so surviving infection was a key determinant in whether someone was able to pass on his or her genes. The authors propose that evolution and genetics have bound together depressive symptoms and physiological responses that were selected on the basis of reducing mortality from infection. Fever, fatigue/inactivity, social avoidance and anorexia can all be seen as adaptive behaviors in light of the need to contain infection, they write.
The theory provides a new explanation for why stress is a risk factor for depression. The link between stress and depression can be seen as the byproduct of a process that preactivates the immune system in anticipation of a wound, they write.Similarly, a disruption of sleep patterns can be seen in both mood disorders and when the immune system is activated. This may come from our ancestors' need to stay on alert to fend off predators after injury, Miller says.
Miller and Raison's theory could also guide future research on depression. In particular, the presence of biomarkers for inflammation may be able to predict whether someone will respond to various treatments for depression.
Miller and Raison are involved in ongoing research on whether certain medications, which are normally used to treat auto-immune diseases, can be effective with treatment-resistant depression.

Depression is always tied to inflammation. Even someone who suffers from depression, due to life events or stress, will still show inflammatory markers. There really is no separation between mind and body. It's impossible to have any kind of psychological state, without a correlating neurological equivalent.

This raises the question if inflammation alone can also lead to depression. However, their statement is not easy to prove in my eyes. How do they test for infections? There are probably thousands of different infections and I highly doubt that we have the diagnostic means to test for all of them. In the end however it's still very interesting that depression can be absolutely independent from psychological factors. Depression can be a pure physical disease and nothing else.

Click to expand...

It is actually easy as has already been proven for at least one 'type' of inflammation, ie one type of inflammatory cytokine - Interferon treatment is well know to cause depression/mood disorders in those undergoing Hep C treatment (most likely via messing up IDO/serotonin pathway).

It is actually easy as has already been proven for at least one 'type' of inflammation, ie one type of inflammatory cytokine - Interferon treatment is well know to cause depression/mood disorders in those undergoing Hep C treatment (most likely via messing up IDO/serotonin pathway).

ETA 'observed' probably a better word than 'proven' in sentence above

Click to expand...

That's interesting. What I wanted to say was that it's probably not very easy to prove that someone has no infection because we still lack proper diagnostic tests for infections.

That's interesting. What I wanted to say was that it's probably not very easy to prove that someone has no infection because we still lack proper diagnostic tests for infections.

Click to expand...

Yes, it's impossible to prove a negative. No matter how good pathogen detection gets, there is always the theoretical possibility that some are missed. So in essence this is not a scientific question, because it cannot be falsified. OTOH, it is proven, as natasa mentioned, that inflammation without accompanying infection can induce depression.

Thanku for taking the time to highlight this study Waverunner... I found it really fascinating... I haven't come across these evolutionary theories before... I also haven't seen very much research that links depression to inflammation, although I was aware of theory.

The theory that depression is the immune system stuck in the "on" position or "sickness behavior" has been around for a decade as discussed here.

Click to expand...

Waverunner]Yes but it didn't get the attention it deserved. The more studies we see about this topic said:
↑

So what is, in your eyes, the general opinion about depression?

Click to expand...

I know that question isn't directed towards me, but in my experience, the 'general opinion' about depression is often that it is a psychological reaction to a person's social or physical environment, or an inability to cope with a life-situation, or it is stress-related.

Why is that question aimed at Waverunner? He hasn't said anything about ME in this thread.

What's your opinion?

I would say that ME is primarily an immune-related disease, and secondarily an inflammatory disease.

Click to expand...

I don't see the difference between an immune related, and inflammatory disorder. Could you explain the difference?

I asked waverunner, because he started the thread. So it would be natural if he had some thoughts on it. He is also arguing that depression is purely a physical disorder, mediated by the immune system, and involving inflammation, and the same could be said about CFS/ME, so I wondered how he would differentiate the two?

I asked waverunner, because he started the thread. So it would be natural if he had some thoughts on it. He is also arguing that depression is purely a physical disorder, mediated by the immune system, and involving inflammation, and the same could be said about CFS/ME, so I wondered how he would differentiate the two?

Click to expand...

Well, I guess there can be different types of inflammation and immune system abnormalities, and different causes for each.

I doubt if many of us are able to differentiate between depression and ME at a biological level!

My brain doesn't like reading about the details of which cytokines are raised or lowered in relation to ME, so I can never remember any details.

And even the best specialist researchers don't have an understanding of the entire biological nature of either disease. They only have limited insight.

Well, I don't have the answer, either. But understanding what differentiates the disorders might shed some light on their origins. The closest thing to an explanation I've seen is this study:

"Abstract

There is a significant 'comorbidity' between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy. This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2'-5' oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS. Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways. Depression and ME/CFS are not 'comorbid' disorders, but should be regarded as 'co-associated disorders' that are clinical manifestations of shared pathways.

Well, I don't have the answer, either. But understanding what differentiates the disorders might shed some light on their origins. The closest thing to an explanation I've seen is this study:

"Abstract

There is a significant 'comorbidity' between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy. This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2'-5' oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS. Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways. Depression and ME/CFS are not 'comorbid' disorders, but should be regarded as 'co-associated disorders' that are clinical manifestations of shared pathways.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID 20609377 [PubMed - indexed for MEDLINE]"

Click to expand...

That's very interesting thank you adreno.
It's unfortunate that it can't tell us what the underlying causes of the abnormalities are.

That's very interesting thank you adreno.
It's unfortunate that it can't tell us what the underlying causes of the abnormalities are.

Click to expand...

Well, I'm not an expert, but maybe someone would be able to infer something from the pathways involved (synthetase/rnase). I haven't read the full text yet, as my computer broke down and I'm typing this on my phone, but I'll take a look at it later and see if I find something interesting.

And if depression = sickness behavior (inflammatory disorder), what is the difference between depression and CFS, in your opinion?

Click to expand...

In my eyes CFS is a syndrome and is accompanied by many symptoms including depression in some. I do think that depression in CFS is caused by inflammation following a change in the immune system and maybe the bad situation every PWC finds himself in. I do not believe that CBT and GET are of any help.

The general opinion about depression is that it has psychological origin and should be treated as psychological disease only. I agree with what Bob said.

In my eyes CFS is a syndrome and is accompanied by many symptoms including depression in some. I do think that depression in CFS is caused by inflammation following a change in the immune system and maybe the bad situation every PWC finds himself in. I do not believe that CBT and GET are of any help.

The general opinion about depression is that it has psychological origin and should be treated as psychological disease only. I agree with what Bob said.

Click to expand...

Well, there are things that don't fit together here. In major depression disorder, CBT and exercise has both been shown as effective treatments. So why wouldn't it work for CFS, if the inflammatory pathways involved are almost similar?

If you say that depression in CFS, is inflammatory, caused by a change in the immune system, then it is the same as the kind of depression in the study you posted. And as you stated, there is only one kind of depression, the physiological one, again described in the evolutionary study. So how come that CBT and excercise works for inflammatory depression (as described in the study), but not the inflammatory depression seen in CFS? They are both of physiological origin, caused by inflammation, brought on by immune system changes.

So either you are wrong, or the study you posted is wrong. I suggest it's the study.

I'm not sure I agree that the general consensus is that depression is caused by purely psychological factors. This is not what psychiatry believes, and that reasoning would not have lead to the use of chemical antidepressants. For at least 50 years, antidepressants have been in use. I would think that the general opinion is that depression is caused by a chemical imbalance in the brain, usually directly translatable to the monoamine hypothesis, which has prevailed in psychiatry for decades. That is the old hypothesis, and the present one subscribes to the idea of neurodegeneration, which is again ameliorated by antidepressants (or CBT and exercise).

What I believe is the case, is that the evolutionary study in reality describes sickness behavior, which has many of the same symptoms as depression, but is yet different. Sickness behavior follows an infection, and infection is not involved in major depression disorder. But infection is likely involved in CFS. So, in essence, there are more similarities between sickness behavior and CFS, than there are between sickness behavior and depression.

That is also, I argue, why CBT and exercise works in depression, but not in CFS. It doesn't work for sickness behavior, either. So in my view, the theory that depression = sickness behavior, is false. There is also plenty of evidence showing that prolonged psychological stress can lead to depression, without any infection involved. In essence, stress can lead to inflammation and neurodegeneration. Genetic factors are likely involved in this.

Anyone noticed the link http://clinicaltrials.gov/ct2/show/NCT00463580#miller infliximab depressionto the clinical trial of infliximab in major depression? It's especially interesting because that study is completed and the authors speculate wether auto-immune medications may benefit people with treatment resistant depression. In other words, it's very likely that study is 'positive'.

Edit: just to clarify, the authors of this trial are the same ones that published the paper in the OP.

Anyone noticed the link http://clinicaltrials.gov/ct2/show/NCT00463580#miller infliximab depressionto the clinical trial of infliximab in major depression? It's especially interesting because that study is completed and the authors speculate wether auto-immune medications may benefit people with treatment resistant depression. In other words, it's very likely that study is 'positive'.

Click to expand...

We shouldn't forget that standard antidepressants are also anti-inflammatory. But drugs like infliximab are likely more powerful in suppressing the inflammation. The also carry more risks, though. It's an interesting development.

On the other hand, standard anti-inflammatory drugs like ibuprofen hasn't shown efficacy in treating depression. There are likely more factors than inflammation involved in depression, like neurodegeneration, and HPA axis dysfunction. Antidepressants like SSRIs, besides their anti-inflammatory action, also normalize HPA axis function, and increase neurogenesis.